Compositions and methods for inhibiting protein on surfaces

ABSTRACT

The use of NIPAM polymers to prevent or reduce the formation of protein deposits on the surfaces of medical devices is described. The invention is particularly directed to reduction of the adsorption of proteins on surfaces of contact lenses and other medical prosthetics.

CLAIM FOR PRIORITY

This application is a continuation of patent application Ser. No.11/273,778, filed Nov. 15, 2005, now allowed, which is a continuation ofpatent application Ser. No. 10/732,934, filed Dec. 11, 2003, whichclaims priority under 35 USC §119(e) from Provisional Application Ser.No. 60/436,159 filed Dec. 23, 2002.

BACKGROUND OF INVENTION

The present invention is directed to the reduction of protein depositionon surfaces. The invention provides compositions and methods forinhibiting the deposition of protein on the surfaces of medical devices,particularly biomedical and prosthetic devices. The invention is basedon the discovery that certain polymers and related copolymers comprisingthe monomer n-isopropylacrylamide (NIPAM) significantly inhibit proteindeposition on the surfaces of contact lenses.

Proteins adsorb to almost all surfaces and the minimization orelimination of protein adsorption has been the subject of numerousstudies, such as those reported by Lee, et al., in J. Biomed. MaterialsRes., vol. 23, pages 351-368 (1989). Sensors, chromatographic supports,immunoassays, membranes for separation, biomedical implants, prostheticdevices (e.g., contact lenses) and many other devices or objects can beadversely affected by protein adsorption. A method and/or means fortreating the surfaces of such objects so as to prevent or reduce proteindeposition would therefore be quite advantageous.

The use of NIPAM-containing polymers to modify surfaces and controlprotein deposition on glass and silicon substrates has been previouslydescribed. The following publications provide further backgroundregarding such modifications:

1. Kidoki, et al., Lanqmuir, 17, pp. 2402-2407 (2001);

2. Bohanon, et al., J. Biomater. Sci. Polymer Edn., Vol. 8, No. 1, pp.19-39 (1996);

3. International (PCT) Patent Publication No. WO 02/30571 A2 (Sudor);

4. U.S. Pat. No. 6,447,897 (Liang, et al.);

5. U.S. Pat. No. 6,270,903 (Feng, et al.); and 6. Huber, et al.,Science, Vol. 301, pp. 352-354, Jul. 18, 2003.

The above-identified publications do not disclose or suggest thatNIPAM-containing polymers could be used to modify the surfaces ofmedical devices, such as contact lenses, and to control proteindeposition and release on such surfaces.

The terms “soft” and “hard” relative to contact lenses are generallyassociated with not only the relative hardness of the respective typesof lenses, but also the type of polymeric material from which the lensesare formed. The term “soft” generally denotes a contact lens that isformed from a hydrophilic polymeric material, such as hydroxyethylmethacrylate or “HEMA”, while the term “hard” generally denotes a lensthat is formed from a hydrophobic polymeric material, such aspolymethylmethacrylate or “PMMA”. The surface chemistry and porosity ofthe hard and soft lenses is quite different. Soft lenses typicallycontain a large amount of water, are quite porous, and bear ioniccharges on the exposed surfaces of the lenses, while hard lenses areconsiderably less porous and generally do not bear ionic surfacecharges.

The ionic surfaces and porous nature of soft contact lenses can lead tosignificant problems when the lenses come into contact with the tearfilm due to the complex composition of the tear film, which is largelycomprised of proteins, lipids, enzymes and various electrolytes. Tearcomponents include albumin, lactoferrin, lysozyme and a number ofimmunoglobulins. The uptake of proteins from the tear fluid onto thelens is a common problem and depends on a number of factors, includingthe nature of the materials from which the lens is made.

Soft contact lenses act as efficient substrates for protein depositionand adsorption. This fouling can lead to dehydration of the lens andinstability of the tear film, resulting in discomfort and lack oftolerance in the wearer. Adsorption of proteins can also facilitatebacterial colonization and this can increase the risk ofvision-threatening infections.

In view of the potential fouling of contact lenses and the problemscreated by such fouling, as discussed above, it is generally acceptedthat contact lens cleaning must be a regular part of a patient's lenscare regimen. Many different types of cleaning agents have been utilizedin the past for this purpose. Cleaning agents such as surfactants andenzymes are typically incorporated into contact lens care products toremove protein deposits. However, the use of these agents can lead toirritation, and in cases where rubbing and cleaning regimens arerequired, there is a possibility that the cleaning agents will not beused properly or will be used in a manner that damages the lenses. Inview of the foregoing problems, it would be advantageous if the surfacesof contact lenses could be modified so as to prevent or reduce theadsorption of proteins to the surfaces.

Various attempts have been made to reduce protein deposit formation oncontact lenses. The following patents may be referred to for furtherbackground regarding such attempts:

U.S. Pat. No. 4,411,932 describes the use of polymeric alcohols andpolymeric ethers, including poly(ethylene glycol), polyethylene oxideand polyethylene glycol methyl ether, as prophylactic agents againstsoilant deposits on contact lenses;

U.S. Pat. No. 6,274,133 (Hu et al.) describes the use of cationiccellulose polymers to prevent the build-up of lipids and proteins on asilicone-hydrogel lens;

U.S. Pat. No. 6,323,165 (Heiler, et al.) describes the use of chargedpolyquaternium polymers to block the binding of proteins to hydrophiliccontact lenses; and

U.S. Pat. No. 6,096,138 (Heiler, et al.) describes the use ofpolyquaternium polymers such as Luviquat® (BASF), which is a mixture ofvinylpyrrolidone and vinylimidazolium moieties that can bind tohydrophilic contact lens materials, so as to block the binding ofproteinaceous materials to the lenses.

These prior attempts to reduce protein binding have drawbacks. Forexample, cationic polymers may act as irritants upon contact with theeye when utilized at high concentrations. Additionally, due to thepositive charge character of these macromolecules, complex formationwith anionic surfactants or other components of CLC products may lead toflocculation and phase separation in the formulation, which is asignificant problem. Accordingly, there is need for new approaches toprovide protein resistant surfaces.

Due to the trend toward use of extended wear lenses, it would be usefulto be able to provide contact lens wearers with a contact lens surfacethat inhibits adsorption of proteinaceous matter for extended timeperiods, without compromising the safety of the patient. The polymershould also be compatible in contact lens care solutions when storage,disinfection and/or cleaning are desired by the patient. The presentinvention is directed to satisfying these needs.

SUMMARY OF INVENTION

The present invention is directed to the use of polymers that aresurface active and exhibit a temperature response in aqueous solutions.The polymers and related polymers (e.g., co-polymers) are formed from aN-isopropylacrylamide (“NIPAM”) monomer.

The present invention is based on a discovery that the NIPAM polymersand related polymers may be utilized to inhibit protein deposition onthe surfaces of hydrogel contact lenses. The NIPAM polymers provideunique solution properties, and it has been discovered that theseproperties can be employed in formulations where protein resistanthydrogel surfaces are desired.

As discussed above, there is a need for improved approaches formodifying the adsorption of proteins on the surfaces of contact lenses.The present invention is based on a discovery that the NIPAM polymersdescribed herein are uniquely suited for this purpose.

The NIPAM polymers described herein may be employed in various mannersin order to achieve modification of contact lens surfaces and surfacesof other medical devices. For example, contact lenses can be stored insolutions containing NIPAM polymers prior to being worn. Thisprophylactic approach allows the polymers to form a protective layer onthe surface of the lenses before the consumer even exposes the lenses totear fluids containing protein. The NIPAM polymers may also beincorporated in multi-purpose solutions for treating contact lenses on adaily basis. Chemical grafting on surfaces to form permanent coatings ofNIPAM polymers is another method for preparing protein resistantsurfaces.

In addition to contact lenses, the surface modification techniquesdescribed herein may be applied to various medical devices where proteinresistant surfaces are desired, such as intraocular lenses, catheters,cardiac stents, prosthetics, and other medical devices that undergoprolonged exposure to proteins during use in or on the bodies of humansor other mammals.

Although not wishing to be bound by theory it is believed that the NIPAMpolymers described herein have a range of inherent physical properties(e.g., low interfacial free energy, hydrophilic-hydrophobic properties,very low toxicity, dynamic surface mobility and steric stabilization)that enable these polymers to exhibit superior protein inhibitingcharacteristics.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a graph showing the results of the tests described in Example1; and

FIG. 2 is a graph showing the results of the tests described in Example3.

DETAILED DESCRIPTION OF THE INVENTION

The NIPAM polymers utilized in the present invention have the followingformula:

wherein n is a whole number of from 10 to 3,000.

The NIPAM polymers utilized in the present invention include varioustypes of polymers that comprise the above-described monomer. Thepolymers may be formed entirely from the NIPAM monomer identified above,or other monomers can Is be incorporated into the polymer bycopolymerizing the NIPAM monomer with other monomers, such as acrylicacid, acrylamide, N-acetylacylamide, N,N-dimethylacrylamide and butylmethacrylate. In addition, modified polymers or copolymers containingthe NIPAM monomer can be prepared by functionalization of end groups,preparation of block copolymers, and cross-linking of polymers. All suchpolymers, copolymers or modifications thereof are referred to herein aseither “NIPAM polymers” or “PNIPAM”. The NIPAM polymers utilized in thepresent invention will typically have molecular weights of from 1,000 to300,000 Daltons. The polymers are available from Polymer Source, Inc.,Dorval, Quebec (Canada).

The amount of PNIPAM utilized in the compositions of the presentinvention will vary depending on the form of the compositions and theintended use thereof. The concentration of PNIPAM utilized willgenerally be an amount sufficient to obtain a solution surface tensionof less than 50 milliNewtons per meter (“mNm⁻¹”) at room temperature(23° C.).

The above-described NIPAM polymers are surface active, and thereforewill readily adsorb to most types of surfaces. Factors such as the typeof surface (hydrophobic versus hydrophilic), temperature, buffer andexcipients will influence the interaction between the polymers and asurface, and will influence the magnitude of the interactions.

The above-described PNIPAM polymers may be combined with othercomponents commonly utilized in products for treating contact lenses,such as rheology modifiers, enzymes, antimicrobial agents, surfactants,chelating agents or combinations thereof. The preferred surfactantsinclude anionic surfactants, such as RLM 100, and nonionic surfactants,such as the poloxamines available under the name “Tetronic®”, and thepoloxamers available under the name “Pluronic®”. Furthermore, a varietyof buffering agents may be added, such as sodium borate, boric acid,sodium citrate, citric acid, sodium bicarbonate, phosphate buffers andcombinations thereof.

The compositions of the present invention that are intended for use asCLC products will contain one or more ophthalmically acceptableantimicrobial agents in an amount effective to prevent microbialcontamination of the compositions (referred to herein as “an amounteffective to preserve”), or in an amount effective to disinfect contactlenses by substantially reducing the number of viable microorganismspresent on the lenses (referred to herein as “an amount effective todisinfect”).

The levels of antimicrobial activity required to preserve ophthalmiccompositions from microbial contamination or to disinfect contact lensesare well known to those skilled in the art, based both on personalexperience and official, published standards, such as those set forth inthe United States Pharmacopoeia (“USP”) and similar publications inother countries.

The invention is not limited relative to the types of antimicrobialagents that may be utilized. Examples of antimicrobial agents that maybe used include: chlorhexidine, polyhexamethylene biguanide polymers(“PHMB”), polyquaternium-1, and the amino biguanides described inco-pending U.S. patent application Ser. No. 09/581,952 and correspondingInternational (PCT) Publication No. WO 99/32158, the entire contents ofwhich are hereby incorporated in the present specification by reference.

The preferred antimicrobial agents are polyquaternium-1, and aminobiguanides of the type described in U.S. patent application Ser. No.09/581,952 and corresponding International (PCT) Publication No. WO99/32158. The most preferred amino biguanide is identified in U.S.patent application Ser. No. 09/581,952 as “Compound Number 1”. Thiscompound has the following structure:

It is referred to below by means of the code number “AL-8496”.

The ophthalmic compositions of the present invention will generally beformulated as sterile aqueous solutions. The compositions must beformulated so as to be compatible with ophthalmic tissues and contactlens materials. The compositions will generally have an osmolality offrom about 200 to about 400 milliosmoles/kilogram water (“mOsm/kg”) anda physiologically compatible pH.

The compositions of the present invention and the ability of thosecompositions to reduce protein adsorption on contact lenses are furtherillustrated by the following Examples. Unmodified (i.e., non-ionic)NIPAM polymers and modified (i.e., end terminated with —COOH groups)NIPAM polymers were added to appropriately buffered solutions todemonstrate the ability of these polymers to reduce protein adsorptionwhen utilized as components of buffered multi-purpose solutions fortreating contact lenses. A simple means of producing PNIPAM-modifiedsurfaces was used in order to mimic the contact lensdisinfection/cleaning regime typically used by the consumer.

EXAMPLE 1

The tests described below were conducted to evaluate the ability ofNIPAM polymers to modify contact lens surfaces and thereby reduceprotein adsorption.

Materials/Methods

The materials and methods utilized in the evaluation were as follows:

Chemicals

Lysozyme (Sigma, Chicken egg white, grade 1, 3x crystalline),Trifluoroacetic Acid Anhydrous (Sigma, Protein sequencing grade)Acetonitrile (EM Science, HPLC grade), Sodium Phosphate Monobasic,Monohydrate (Sigma, ACS reagent grade), Sodium Phosphate Dibasic,Anhydrous (Sigma, ACS reagent grade), Sodium Chloride (Sigma, ultra puregrade), Unisol®4 (Alcon Laboratories, Inc., preservative-free.pH-balanced saline solution for rinsing)

The NIPAM polymers utilized are identified in Table 1 below. Thesepolymers were purchased from Polymer Source Inc. and were used withoutfurther purification.

TABLE 1 Polymer Type M_(v) × 10³ M_(w)/M_(n) P2991-NIPAM Non-ionic46,380 2.36 P604-NIPAM Non-ionic 71,600 2.44 P1239-NIPAM Non-ionic122,000 2.50 P2426F2-NIPAM-COOH Anionic 132,000 1.29

Lenses

Acuvue (Vistakon, a division of Johnson & Johnson Vision Products, Inc)lenses were used as the substrate in this study. The lenses had thefollowing parameters: 42% etafilcon A, 58% water, FDA Group IV lens.Diameter, 14.0 mm; base curve, 8.8 mm; power, −2.00.

Formulations

The NIPAM and NIPAM-COOH polymers identified in Table 1 were formulatedat pH 7.8 in a buffered vehicle containing 1.5% sorbitol, 0.6% boricacid and 0.32% NaCl. In a beaker, all the formulation chemicals exceptfor the NIPAM polymers were weighed out and purified water was added (QSto 95%). The pH was adjusted to 7.8 with NaOH/HCl. The NIPAM polymer wasweighed out and added to the buffer solution and this was stirredovernight to solubilize the polymer. The test formulations are shown inTable 2 below; the concentrations are expressed as weight/volume percent(“w/v%”):

TABLE 2 Formulation Numbers 9591-47C Component 9591-47A 9591-47B(Control) P2991-NIPAM 0.034 0.017 — Sorbitol 1.5 1.5 1.5 Boric Acid 0.60.6 0.6 Sodium Chloride 0.32 0.32  0.32 Purified Water QS QS QS pH 7.87.8 7.8The test formulations were evaluated for their prophylaxis behaviorusing lysozyme as the model protein, as described below.

Preparation of Deposition Solution Phosphate Buffered Saline (PBS) 1.311g of monobasic sodium phosphate (monohydrate), 5.74 g of dibasic sodiumphosphate (anhydrous), and 9.0 g of sodium chloride were dissolved indeionized water and the volume was brought to 1000 mL with deionizedwater, and pH was adjusted (as necessary). The final concentrations ofsodium phosphate and sodium chloride were 0.05 M and 0.9%, respectively.The final pH was 7.4.

Lysozyme Solution

A 1.5-mg/mL lysozyme solution was prepared by dissolving 750 mg oflysozyme in 500-mL phosphate buffered saline pH adjusted to 7.4.

Lens Extraction Solution (ACN/TFA)

A lens extraction solution was prepared by mixing 1.0 ml oftrifluoroacetic acid with 500-mL acetonitrile and 500 ml of deionizedwater. The pH of the solution ranged from 1.5 to 2.0.

Lens Presoak Procedure

Each lens was immersed in 3-mL of each test formulation and allowed tosit at room temperature overnight. The next morning, the lenses wereremoved from the test formulations and dabbed lightly on a towel.

Lens Deposition Procedure (Physiological Deposition Model)

Each presoaked lens was immersed in a Wheaton glass sample vialcontaining 3-mL of lysozyme solution. The vial was closed with a plasticsnap cap and incubated in a constant temperature water bath at 37° C.for 24 hours. Three additional lenses were included as controls toestablish the total amount of lysozyme deposited. After incubation, thedeposited lenses were removed from their vials and rinsed by dippinginto three consecutive beakers containing 200 ml Unisol®4 or water toremove any excess of the deposition solution.

Extraction and Determination of Lysozyme Extraction

The lenses were extracted with 5 ml of ACN/TFA extraction solution in ascrew-capped glass scintillation vial. The extraction was done byshaking the vial with a rotary shaker (Red Rotor) at room temperaturefor at least 2 hours (usually overnight).

Calculations for the Determination of Lysozyme

Quantitative determination of the lysozyme of the lens extract wascarried out using a fluorescence spectrophotometer interfaced with anautosampler and a computer. The fluorescence intensity of a 2 ml aliquotfrom each sample solution was measured by setting theexcitation/emission wavelength at 280 nm/346 nm with excitation/emissionslits of 2.5 nm/10 nm, respectively, and the sensitivity of thephotomultiplier was set at 950 volts.

A lysozyme standard curve was established by diluting the lysozyme stocksolution to concentrations ranging from 0 to 40 μg/ml, using the ACN/TFAextraction solution for the lens extract and the vehicle for the soakingsolutions. The instrument settings for measuring the fluorescenceintensity were the same for the lens extracts and lens soakingsolutions.

The lysozyme concentrations for all of the samples were calculated basedon the slope developed from the linear lysozyme standard curve. The %prophylaxis of each formulation was calculated by subtracting the amountof lysozyme in the lens extract from the amount of lysozyme from thecontrol lenses (total deposit), then dividing that by the total depositand multiplying by 100.

Results

FIG. 1 shows the % prophylaxis as a function of PNIPAM concentration(g/100 ml) for nonionic NIPAM polymers having molecular weights of46,380; 71,600; and 122,000, respectively.

FIG. 1 shows that there was no significant PNIPAM molecular weightdependence on the % prophylaxis using the defined polymerconcentrations. PNIPAM concentrations up to 0.2 g/100 ml gave %prophylaxis results of approximately 30%. With increasing PNIPAMconcentrations above 0.2 g/100 ml the % prophylaxis could be increasedto 50% to 60% using polymer concentrations between 0.4 g/100 ml and 0.65g/100 ml. The % prophylaxis was not dependent on the molecular weight ofthe NIPAM polymers.

EXAMPLE 2

The prophylactic properties of NIPAM polymers were further evaluatedusing a 3-day cycling study. Two sets of lenses were prepared. One setwas presoaked in the formulations shown in Table 2 before going into thelysozyme solution, whereas the other set was not. Both sets of lenseswere then placed in the lysozyme solution for 8 hours (Day 1). At theend of the day all the lenses were rinsed and put in their respectiveformulations to soak overnight. The following day (Day 2), the lenseswent back into the lysozyme for the day (8 hours). This was repeated tocomplete 3 cycles (3 Days). At the end of the experiment all the lenseswere analyzed in accordance with the procedures described in Example 1.The results are presented in Table 3;

TABLE 3 Uptake of Amount Lysozyme Removed % Sample (ug/lens) sd(ug/lens) Prophylaxis sd 9591- 124.1 9.1 261.9 67.8 0.8 47A(PS) 9591-151.5 3.9 234.5 60.8 0.6 47B(PS) 9591- 386.0 6.1 — — — 47C(PS) 9591-47A206.3 2.7 174.9 45.9 1.2 9591-47B 221.3 10.4 159.9 41.9 0.9 9591-47C381.2 7.1 — — — PS = Presoaked

The results demonstrate that the buffered solutions containing a NIPAMpolymer (i.e., P2991-NIPAM) were effective in reducing protein uptake inboth the presoaked and non-presoaked lenses. For example, the presoakedlenses treated with solutions containing concentrations of 0.034% and0.017% of the NIPAM polymer demonstrated prophylaxis values of 67.8% and60.8%, respectively. For the non-presoaked lenses the prophylaxis valueswere 45.9% and 41.9% at concentrations of 0.034% and 0.017%,respectively.

The results set forth in Table 3 demonstrate that treatment of thelenses with a NIPAM polymer solution prior to exposure to proteins ispreferable. However, the results also show that even when the lenseshave already been exposed to proteins prior to an initial treatment witha NIPAM polymer solution, the uptake of protein is reduced when thelenses are subsequently treated with a NIPAM polymer solution. Thus, theresults of this study confirm that the compositions of the presentinvention are effective in reducing the formation of protein deposits oncontact lenses, even when the lenses are repeatedly exposed to proteincontamination.

EXAMPLE 3

The prophylaxis work was extended to formulations containing theantimicrobial agent AL-8496 with unmodified NIPAM (non-ionic) andmodified NIPAM (end functionalized with COOH) polymers. The formulationsevaluated are shown in Table 4, below:

TABLE 4 Formulations for Microbiology Evaluation of PNIPAM FormulationsContaining A Contact Lens Disinfecting Agent (AL-8496) FormulationNumbers 9591- 9591- 9591- 9591- 9591-44I Component 44B 44C 44D 9591-44E44F (Control) P2991- 0.087 0.21 NIPAM P2426F2- 0.040 0.10 0.25 NIPAMCOOHAL-8496* 0.0004 0.0004 0.0004 0.0004 0.0004 0.0004 Tetronic ® 0.1 0.10.1 0.1 0.1 0.1 1304 Sorbitol 0.4 0.4 0.4 0.4 0.4 0.4 Sodium 0.2 0.2 0.20.2 0.2 0.2 borate Sodium 0.6 0.6 0.6 0.6 0.6 0.6 citrate Propylene 1.01.0 1.0 1.0 1.0 1.0 glycol Disodium 0.05 0.05 0.05 0.05 0.05 0.05edetate pH 7.8 7.8 7.8 7.8 7.8 7.8 % 37.4 ± 0.2 54.1 ± 1.0 51.0 ± 0.557.3 ± 0.4 62.8 ± 1.2 0.6 ± 0.0 Prophylaxis *As base

The procedures utilized were the same as in Example 1. FIG. 2 shows theprophylaxis data obtained using the overnight soak model with lensespre-soaked in the respective PNIPAM formulations.

FIG. 2 shows that the prophylaxis properties of the NIPAM polymers wereretained in the presence of the antimicrobial agent AL-8496 and otherformulation components, including cleaning ingredients (e.g., citrateand Tetronic® 1304). The data demonstrate that both unmodified andmodified NIPAM polymers can be incorporated into multi-purpose contactlens care formulations without compromising the prophylactic propertiesof the polymers.

EXAMPLE 4

The disinfection activity of the formulations shown in Table 4 above wasalso evaluated. The results are shown in Table 5 below.

TABLE 5 Disinfection Properties of PNIPAM Formulations containingAL-8496 Time 9591- 9591- 9591- 9591- 9591- 9591- Microorganism (hrs) 44B44C 44D 44E 44F 44I Candida 6 2.8 3.0 3.0 3.4 3.2 3.0 albicans 24 3.94.5 6.0 6.0 5.3 6.0 Serratia 6 2.7 6.2 2.8 2.7 2.6 2.6 marcescens 24 5.56.2 5.5 6.2 5.5 4.9 Staphylococcus 6 5.5 4.5 5.5 4.4 4.3 4.9 aureus 246.2 5.0 6.2 6.2 6.2 5.2

The results demonstrate that the NIPAM polymers did not adversely affectthe antimicrobial activity of the antimicrobial agent AL-8496.

EXAMPLE 5

Several formulations were evaluated to compare the prophylaxisproperties of PNIPAM with two well-known block co-polymers, Tetronic®1107 and Pluronic® F127. The formulation components and prophylaxisresults are given in Table 6, below.

The evaluation was carried out using the same procedures as outlined inExample 1. The buffered solution utilized as a control (10581-85J) didnot exhibit any prophylaxis properties. However, as shown in Table 6,the compositions of the present invention containing PNIPAM atconcentrations of 0.2% (10581-85B) and 0.4% (10581-85C) producedprophylaxis results of 56.2% and 63%, respectively.

In contrast, the solutions containing Tetronic® 1107 and Pluronic® F127block co-polymers at concentrations of up to 0.8% did not produce anysignificant prophylaxis.

TABLE 6 10581- 10581- 10581- 10581- 10581- 10581- 10581- Components 85B85C 85E 85F 85H 85I 85J PNIPAM P2991 0.2 0.4 — — — — — Tetronic ® 1107 —— 0.4 0.8 — — — Pluronic ® F127 — — — — 0.4 0.8 — Sorbitol 1.5 1.5 1.51.5 1.5 1.5 1.5 Boric Acid 0.6 0.6 0.6 0.6 0.6 0.6 0.6 Sodium Chloride 0.32  0.32  0.32  0.32  0.32  0.32  0.32 Purified Water QS QS QS QS QSQS QS pH 7.8 7.8 7.8 7.8 7.8 7.8 7.8 % Prophylaxis 56.2 + 0.1 63.0 + 0.40.00 + 2.3 4.1 + 2.2 0.0 + 2.1 0.0 + 0.9 0.8 + 1.0

1. A method of modifying a surface of a contact lens or intraocular lenswhich comprises applying a solution to said surface of said contact lensor intraocular lens, said solution comprising an amount of a NIPAMpolymer and an ophthalmically acceptable vehicle therefore wherein theamount of NIPAM polymer is sufficient to modify said surface such thatadsorption of proteins to said surface in inhibited when the contactlens or intraocular lens and wherein the modification of the surfaceoccurs before the contact lens or intraocular lens exposed to a proteincontaining fluid of a consumer.
 2. The method of claim 1 wherein thesolution contains the NIPAM polymer in an amount sufficient to providethe solution with a surface tension of less than 50 mnM⁻¹ at atemperature of 23° C.
 3. The method of claim 2 wherein the applicationof the solution to said surface modifies said surface so that theadsorption of proteins to said surface is inhibited.
 4. The method ofclaim 3 wherein the solution is a sterile, aqueous solution.
 5. Themethod of claim 4 wherein the solution is a multi-purpose solutionsuitable for treating contact lenses on a daily basis and comprises aneffective amount of a surfactant.
 6. The method of claim 5 wherein thesolution contains an ophthalmically acceptable antimicrobial agent in anamount effective to disinfect a contact lens.
 7. The method of claim 4wherein the solution has a physiologically compatible pH and anosmolality of 200 to 400 mOsm/kg.
 8. The method of claim 1 wherein theprotein containing fluid is a tear fluid.